212 Part II / Cell and Molecular Biology of Cells of the Nervous System
threshold.
1
Third, the action potential is conducted
without decrement. It has a self-regenerative feature
that keeps the amplitude constant, even when it is con-
ducted over great distances. Fourth, the action poten-
tial is followed by a refractory period. For a brief time
after an action potential is generated, the neuron’s abil-
ity to fire a second action potential is suppressed. The
refractory period limits the frequency at which a nerve
can fire action potentials, and thus limits the information-
carrying capacity of the axon.
These four properties of the action potential—
initiation threshold, all-or-none amplitude, conduc-
tion without decrement, and refractory period—are
unusual for biological processes, which typically
respond in a graded fashion to changes in the envi-
ronment. Biologists were puzzled by these properties
for almost 100 years after the action potential was first
recorded in the mid-1800s. Finally, in the late 1940s
and early 1950s, studies of the membrane properties of
the giant axon of the squid by Alan Hodgkin, Andrew
Huxley, and Bernard Katz provided the first quantita-
tive insight into the mechanisms underlying the action
potential.
The Action Potential Is Generated by the Flow
of Ions Through Voltage-Gated Channels
An important early insight into how action potentials
are generated came from an experiment performed by
Kenneth Cole and Howard Curtis that predated the
studies by Hodgkin, Huxley, and Katz. While record-
ing from the giant axon of the squid, they found that the
conductance of the membrane increases dramatically
during the action potential (Figure 10–1). This discov-
ery provided evidence that the action potential results
from a dramatic increase in the ion permeability of the
cell membrane. It also raised two central questions:
Which ions are responsible for the action potential, and
how is the permeability of the membrane regulated?
Hodgkin and Katz provided a key insight into
this problem by demonstrating that the amplitude of
the action potential is reduced when the external Na
+
Figure 10–1 The action potential results from an increase in
ion conductance of the axon membrane.This historic record-
ing from an experiment conducted in 1939 by Kenneth Cole
and Howard Curtis shows the oscilloscope record of an action
potential superimposed on a simultaneous record of axonal
membrane conductance.
动作电位
膜电导
1
The all-or-none property describes an action potential that is gener-
ated under a specific set of conditions. The size and shape of the
action potential can be affected by changes in membrane proper-
ties, ion concentrations, temperature, and other variables, as dis-
cussed later in the chapter. The shape can also be affected slightly
by the current that is used to evoke it, if measured near the point of
stimulation.
concentration is lowered, indicating that Na
+
influx is
responsible for the rising phase of the action potential.
They proposed that depolarization of the cell above the
threshold for an action potential causes a brief increase
in the cell membrane’s Na
+
conductance, during which
the Na
+
conductance overwhelms the K
+
conductance
that predominates in the cell at rest, thereby driving
the membrane potential towards E
Na
. Their data also
suggested that the falling phase of the action potential
was caused by a later increase in K
+
permeability.
Sodium and Potassium Currents Through
Voltage-Gated Channels Are Recorded
With the Voltage Clamp
This insight of Hodgkin and Katz raised a further ques-
tion. What mechanism is responsible for regulating the
changes in the Na
+
and K
+
permeabilities of the mem-
brane? Hodgkin and Andrew Huxley reasoned that
the Na
+
and K
+
permeabilities were regulated directly
by the membrane voltage. To test this hypothesis, they
systematically varied the membrane potential in the
squid giant axon and measured the resulting changes
in the conductance of voltage-gated Na
+
and K
+
chan-
nels. To do this, they made use of a new apparatus, the
voltage clamp, developed by Kenneth Cole.
Prior to the availability of the voltage-clamp tech-
nique, attempts to measure Na
+
and K
+
conductance
as a function of membrane potential had been lim-
ited by the strong interdependence of the membrane
potential and the gating of Na
+
and K
+
channels. For
example, if the membrane is depolarized sufficiently
to open some voltage-gated Na
+
channels, the influx
of Na
+
through these channels causes further depolari-
zation. The additional depolarization causes still more
Kandel-Ch10_0211-0236.indd 212 10/12/20 11:37 AM